The recent availability of the stable cell line MCF-7 which displays the classical steroid receptor mechanisms of "target" tissues provides the investigator with the first opportunity to study hormone responsive cells in a controlled environment. These cells, which were derived from a human breast cancer, will be utilized in investigations designed to learn more of the relationship of steroid hormone conjugation and metabolism to the steroid receptor mediated stimulation of hormone responsive breast tumors. Information which is available from recent experiments in this laboratory and from the literature suggests that the steroid sulfotransferase and dehydrogenase enzymes present in "target" tissues may be involved in limiting the nuclear activity of the hormone. It is proposed to study the relationship of estrogen and androgen sulfation and dehydrogenation to the mechanism of the receptor migration into (or out of?) the nucleus. The observed dependence of estrogen and steroid alcohol sulfotransferase activities (found in target tissues) on the hormonal milieu of the animal will be examined. The influence on the activities of these enzymes by steroid and peptide hormones will be determined in cells grown in chemically defined media. Furthermore, it has been suggested that the steroid alcohol sulfotransferase may be involved in controlling the biosynthesis of steroid hormones. However, the function of this sulfating enzyme in breast tumors is not understood at the present time. The very high activity of steroid alcohol sulfotransferase in MCF-7 cells makes it possible to study, in controlled tissue culture experiments, the involvement of steroid sulfates in the steroid interconversions found in target tissues, particularly breast tumors in which a paraendocrine capacity has been reported.